From its beginnings as a center which focused on behavioral, neuropsychological and neuropsychiatric changes versus the course of the disease, the University of Pittsburgh Alzheimer Disease Research Center (ADRC) has evolved into a broadly based, full-service dementia research center, fulfilling its missions in excellent patient care and follow-up, clinical, basic, and translational research, and education of students, residents, fellows, faculty, community physicians, and the lay community. Our areas of research specialization include neuropsychiatric symptoms and manifestations of Alzheimer's disease and other dementias, neuroimaging and new neuroimaging modalities, genetics, and overlap of Alzheimer's disease with other neurodegenerative disorders. A wide range of basic and clinical research studies are supported by patients, data, or biological materials from the ADRC. In this current renewal, the Center will support 6 cores (including the requisite Data Management and Statistics Core) research projects, and 2 pilot studies. One project will assess the ability to image amyloid in the brains of patients with autosomal dominant familial Alzheimer's disease;a second will evaluate gene therapy of targeted neprilysin enzymes which destroy or accelerate metabolism of beta amyloid, and the third will attempt to develop subhuman primate and human differentiated neural precursors from stem cells for use as models of AD and initiate the development of a transgenic Alzheimer's monkey to advance translational studies of therapies and establish a better animal model of AD. The Pitt ADRC has also provided national and international leadership to the Centers program and other collaborative efforts in Alzheimer's disease, in the ADC directors group, the ADC administrators group, the AD Cooperative Study, and the NACC. Members of the Pittsburgh ADRC sit on or chair advisory committees for a variety of other Alzheimer's centers as well as the national Alzheimer's Association.